title: Pulmonary alveolar proteinosis caused by deletion of the GM-CSFRalpha gene in the X chromosome pseudoautosomal region 1.
abstract: Pulmonary alveolar proteinosis (PAP) is a rare lung disorder in which surfactant-derived lipoproteins accumulate excessively within pulmonary alveoli, causing severe respiratory distress. The importance of granulocyte/macrophage colony-stimulating factor (GM-CSF) in the pathogenesis of PAP has been confirmed in humans and mice, wherein GM-CSF signaling is required for pulmonary alveolar macrophage catabolism of surfactant. PAP is caused by disruption of GM-CSF signaling in these cells, and is usually caused by neutralizing autoantibodies to GM-CSF or is secondary to other underlying diseases. Rarely, genetic defects in surfactant proteins or the common beta chain for the GM-CSF receptor (GM-CSFR) are causal. Using a combination of cellular, molecular, and genomic approaches, we provide the first evidence that PAP can result from a genetic deficiency of the GM-CSFR alpha chain, encoded in the X-chromosome pseudoautosomal region 1.
authors.affiliation: Department of Medicine, Texas A&M College of Medicine, Texas A&M Health Science Center, Houston, TX 77030, USA.
authors.forename: Margarita
authors.initials: M
authors.lastname: Martinez-Moczygemba
authors.forename: Minh L
authors.initials: ML
authors.lastname: Doan
authors.forename: Okan
authors.initials: O
authors.lastname: Elidemir
authors.forename: Leland L
authors.initials: LL
authors.lastname: Fan
authors.forename: Sau Wai
authors.initials: SW
authors.lastname: Cheung
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Lei
authors.forename: James P
authors.initials: JP
authors.lastname: Moore
authors.forename: Ghamartaj
authors.initials: G
authors.lastname: Tavana
authors.forename: Lora R
authors.initials: LR
authors.lastname: Lewis
authors.forename: Yiming
authors.initials: Y
authors.lastname: Zhu
authors.forename: Donna M
authors.initials: DM
authors.lastname: Muzny
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.forename: David P
authors.initials: DP
authors.lastname: Huston
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D002675:Child, Preschool; D041321:Chromosomes, Human, X / Q000235:genetics*; D005091:Exons; D005260:Female; D005838:Genotype; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D011649:Pulmonary Alveolar Proteinosis / Q000235:genetics*; D011663:Pulmonary Surfactants / Q000378:metabolism; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology; D014424:Turner Syndrome
chemical_list: D039481:CD11b Antigen; C521678:CSF2RA protein, human; D011663:Pulmonary Surfactants; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor